# Autoreactive T Cell Function in Vitiligo

> **NIH NIH P50** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $506,937

## Abstract

T cells are effector cells of autoimmunity that migrate to find their targets, produce cytokines that recruit and
activate other immune cells, and destroy their target cells in affected tissue. Vitiligo is an autoimmune disease
of the skin in which cytotoxic CD8+ T cells target pigment-making melanocytes, which results in disfiguring
white spots that are particularly devastating for those with darker skin and thus leads to health disparities for
the most vulnerable of our population. Vitiligo is an ideal disease in which to investigate mechanisms of organ-
specific autoimmunity because disease phenotype can be directly correlated to molecular pathways. That is,
affected skin can be observed and sampled, target cells and antigens are known, and translational research
tools are available. Vitiligo shares genetic risk alleles and other mechanisms with autoimmune diseases like
type 1 diabetes and multiple sclerosis that are more difficult to study in human patients. Through vitiligo we can
develop a comprehensive understanding of organ-specific autoimmunity as it progresses within human tissue.
In vitiligo and models of other human autoimmune diseases, autoreactive T cell responses are commonly char-
acterized as homogenous, with an “all or nothing” result. This is partly due to the fact that mouse models of
autoimmunity are frequently based on a single high-affinity CD8+ cytotoxic clone transferred and activated arti-
ficially. However, we found that T cells infiltrating vitiligo skin lesions are polyclonal and heterogeneous, with
different antigenic specificities and activation states. Cytotoxic CD8+ T cells organize into clustered units within
the epidermis that appear to attack melanocytes, while CD4+ and Treg cells are at the periphery of these clus-
ters. Together, these data indicate that T cell interactions in vitiligo are more complex than previously under-
stood. Our central hypothesis is that polyclonal CD8+, CD4+, and Treg cell communications coordinate mela-
nocyte destruction and determine vitiligo clinical phenotypes.
This project will determine how autoreactive T cell clonal diversity and localization define the clinical disease
phenotype, how T cell subtypes interact with each other to coordinate autoimmunity, and how T cells orches-
trate melanocyte destruction within the skin. First, we will determine the in vivo location, spatial relationships,
and functional characteristics of T cell clones in different clinical phenotypes of vitiligo, such as early incipient
vs. late established lesions, active vs. stable disease, and single vs. multiple locations. Next, we will character-
ize the function and reactivity of T cells isolated directly from the skin of these lesions. We will use primary T
cell and skin organ culture, T cell functional assays, T cell receptor affinity assays, the sequential fluorescence
in situ hybridization (seqFISH+) Core, and advanced computational methods. This project is translational in
approach because it wil...

## Key facts

- **NIH application ID:** 10868481
- **Project number:** 5P50AR080593-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** SALLY Choate KENT
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $506,937
- **Award type:** 5
- **Project period:** 2022-09-12 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868481

## Citation

> US National Institutes of Health, RePORTER application 10868481, Autoreactive T Cell Function in Vitiligo (5P50AR080593-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10868481. Licensed CC0.

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